Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

High levels of all-cause mortality among people who inject drugs from 2018 to 2022.

BACKGROUND: Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022. METHODS: PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. RESULTS: Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. CONCLUSION: Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.

Assessment of dietary habits and the adequacy of dietary intake of patients with cirrhosis-the KIRRHOS study.

BACKGROUND & AIMS: Undernutrition is widely prevalent in patients with cirrhosis and affects prognosis. Given the lack of data regarding the dietary intake (DI) and habits of patients with cirrhosis, the aim of the present study was to evaluate them by assessing diet's adequacy compared to the new guidelines, and the association of DI with nutritional status indicators. METHODS: One hundred and eighty-seven patients (57.8% male, 59.9 ± 10.9 years old, 44.9% decompensated ones) with cirrhosis of various etiologies were enrolled. The patients' DI was assessed using three 24 h recalls, which were analyzed regarding macronutrients' intake, food groups consumption, adherence to the Mediterranean diet and meal patterns. The Goldberg cut-off limits for the ratio of energy intake to resting energy expenditure were used to evaluate dietary underreporting and patients were accordingly classified as low or adequate energy reporters (LERs and AERs). RESULTS: Among the AERs (n = 91, 48.7%) only 29.7% and 31.9% met current recommendations regarding energy and protein intake, accordingly. Patients reported low intake of several healthy food groups and low adherence to the Mediterranean diet. They reported a median of 4.3 eating episodes per day and they frequently omitted late evening snack. Nevertheless, no statistically significant associations were found between parameters of DI and annual and two-year survival. CONCLUSIONS: Low energy reporting was very frequent in this sample of patients with liver cirrhosis. Diet quality was rather poor, whereas energy and protein intakes were lower than those recommended.

Validation of cutoffs for skeletal muscle mass index based on computed tomography analysis against dual energy X-ray absorptiometry in patients with cirrhosis: the KIRRHOS study.

BACKGROUND: Accurate assessments of muscle mass in patients with cirrhosis are necessary in clinical practice. Computed tomography (CT) of the upper abdomen has been proposed as a useful method for quantifying muscle mass. Recently, Carey et al developed specific cutoffs for muscle wasting based on the skeletal muscle index at the L3 vertebra (L3-SMI) for cirrhotic patients. The aim of the present study was to assess the concurrent validity of the newly proposed cutoffs of Carey et al, along with others widely used in several clinical contexts, using dual energy X-ray absorptiometry (DXA) as the reference method. METHODS: Data were evaluated from 97 Caucasian patients (59.8% male, 59.1±11.6 years old, 45.4% decompensated) with cirrhosis of various etiologies. Muscle mass was assessed using the appendicular lean mass index (ALMI) by DXA and the L3-SMI by CT. Low L3-SMI was defined in relation to 5 different cutoffs. RESULTS: Low muscle mass prevalence was 13.4% according to ALMI and 26.8-45.4% according to the different cutoffs applied for L3-SMI. The Carey et al, Prado et al and Montano-Loza et al cutoffs showed similar sensitivity (all 69.2%) and specificity (79.8%, 76.2% and 75.0%, respectively) and high accuracy (78.4%, 75.3% and 74.2%). The Carey et al cutoffs showed the highest diagnostic validity against DXA the multivariate odds ratio adjusted for age, sex, body mass index category, disease etiology and model for end-stage liver disease score (95% confidence interval) was 5.88 (1.36-25.4), P=0.018. CONCLUSION: Compared to DXA, the cutoffs for identifying muscle wasting proposed by Carey et al were proven to be the most accurate.

Evaluation of the effectiveness of eight screening tools in detecting risk of malnutrition in cirrhotic patients: the KIRRHOS study.

Malnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5-54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.

Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial.

Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD). This randomised controlled single-blind clinical trial investigated the effect of Mediterranean diet (MD) or Mediterranean lifestyle, along with weight loss, in NAFLD patients. In all, sixty-three overweight/obese patients (50 (sd 11) years, BMI=31·8 (sd 4·5) kg/m2, 68 % men) with ultrasonography-proven NAFLD (and elevated alanine aminotransferase (ALT) and/or γ-glutamyl transpeptidase (GGT) levels) were randomised to the following groups: (A) control group (CG), (B) Mediterranean diet group (MDG) or (C) Mediterranean lifestyle group (MLG). Participants of MDG and MLG attended seven 60-min group sessions for 6 months, aiming at weight loss and increasing adherence to MD. In the MLG, additional guidance for increasing physical activity and improving sleep habits were given. Patients in CG received only written information for a healthy lifestyle. At the end of 6 months, 88·8 % of participants completed the study. On the basis of intention-to-treat analysis, both MDG and MLG showed greater weight reduction and higher adherence to MD compared with the CG (all P<0·05) at the end of intervention. In addition, MLG increased vigorous exercise compared with the other two study groups (P<0·001) and mid-day rest/naps compared with CG (P=0·04). MLG showed significant improvements in ALT levels (i.e. ALT<40 U/l (P=0·03) and 50 % reduction of ALT levels (P=0·009)) and liver stiffness (P=0·004) compared with CG after adjusting for % weight loss and baseline values. MDG improved only liver stiffness compared with CG (P<0·001) after adjusting for the aforementioned variables. Small changes towards the Mediterranean lifestyle, along with weight loss, can be a treatment option for patients with NAFLD.

Serum levels of vascular endothelial growth factor in non-alcoholic fatty liver disease.

BACKGROUND: This study aimed to assess the significance of serum levels of vascular endothelial growth factor (VEGF) in non-alcoholic fatty liver disease (NAFLD). METHODS: Sixty-seven consecutive NAFLD patients and 47 healthy controls who visited our liver clinics between May 2008 and December 2010 were included. The NAFLD diagnosis required elevated alanine aminotransferase and/or gamma-glutamyl transpeptidase levels, evidence of hepatic steatosis on ultrasound and/or liver histology, and exclusion of other causes of liver injury. Serum VEGF levels were determined by an enzyme immunoassay. Liver biopsy was obtained in 34 NAFLD patients. Histological lesions were scored by a liver histopathologist. RESULTS: Serum VEGF levels tended to be lower in matched NAFLD patients than in healthy controls (296±146 vs. 365±186 pg/mL, P=0.092); levels in patients with non-alcoholic steatohepatitis (NASH) also tended to be lower than in those with simple fatty liver (FL) (279±149 vs. 359±190 pg/mL, P=0.095); while VEGF levels were significantly lower in NASH patients than in healthy controls (279±149 vs. 365±186 pg/mL, P=0.041). VEGF levels offered poor predictability for the differentiation between NAFLD patients and controls or between NASH and FL patients. However, patients with high VEGF levels (≥300 pg/mL) were significantly more likely to have FL, either in the total NAFLD population (67% vs. 35%, P=0.019) or in the 34 NAFLD patients with liver biopsy (57% vs. 15%, P=0.023), while those with high VEGF levels also had a significantly lower mean fibrosis score (0.7±0.9 vs. 1.6±1.0, P=0.017). CONCLUSION: Our data suggest that serum VEGF levels are equally high in healthy controls and in patients with simple fatty liver, but tend to decrease when NASH develops.

A "healthy diet-optimal sleep" lifestyle pattern is inversely associated with liver stiffness and insulin resistance in patients with nonalcoholic fatty liver disease.

Several lifestyle habits have been described as risk factors for nonalcoholic fatty liver disease (NAFLD). Given that both healthy and unhealthy habits tend to cluster, the aim of this study was to identify lifestyle patterns and explore their potential associations with clinical characteristics of individuals with NAFLD. One hundred and thirty-six consecutive patients with ultrasound-proven NAFLD were included. Diet and physical activity level were assessed through appropriate questionnaires. Habitual night sleep hours and duration of midday naps were recorded. Optimal sleep duration was defined as sleep hours ≥ 7 and ≤ 9 h/day. Lifestyle patterns were identified using principal component analysis. Eight components were derived explaining 67% of total variation of lifestyle characteristics. Lifestyle pattern 3, namely high consumption of low-fat dairy products, vegetables, fish, and optimal sleep duration was negatively associated with insulin resistance (ß = -1.66, P = 0.008) and liver stiffness (ß = -1.62, P = 0.05) after controlling for age, sex, body mass index, energy intake, smoking habits, adiponectin, and tumor necrosis factor-α. Lifestyle pattern 1, namely high consumption of full-fat dairy products, refined cereals, potatoes, red meat, and high television viewing time was positively associated with insulin resistance (ß = 1.66, P = 0.005), although this association was weakened after adjusting for adiponectin and tumor necrosis factor-α. A "healthy diet-optimal sleep" lifestyle pattern was beneficially associated with insulin resistance and liver stiffness in NAFLD patients independent of body weight status and energy intake.

Adherence to follow-up and treatment recommendations in Greek and immigrant patients with chronic hepatitis B in Greece.

BACKGROUND/AIM: Immigrants have multiple barriers to access to health care systems. We evaluated the adherence to follow-up and treatment recommendations of chronic hepatitis B virus (HBV) Greek and immigrant patients. METHODS: In total, 1001 consecutive adult patients with chronic HBV infection who visited our clinics for the first time between 2002 and 2011 were included. All patients born outside Greece were considered immigrants. Diagnosis was considered to be complete if patients could be classified into HBeAg-positive chronic hepatitis B (CHB), inactive carriers, HBeAg-negative CHB, or decompensated cirrhosis. RESULTS: Of the patients, 56% were Greeks and 44% were immigrants. Greeks visited our clinics at a significantly older mean age (50 vs. 35 years, P<0.001) and more frequently with advanced liver disease (11.4 vs. 6.4%, P=0.007). During the first year, Greeks more frequently had several tests and eventually a complete diagnosis (68 vs. 55%, P<0.001). Greeks were more frequently in the phase of HBeAg-negative CHB and less frequently in the phase of inactive carrier or HBeAg-positive CHB, but age was the main determinant for these differences in multivariate analysis. Treatment was initiated more frequently by Greeks than immigrants with treatment indications (86 vs. 65%, P<0.001). Only 30-33% of treated and 4-10% of untreated patients remained under follow-up at year 5, without significant differences between Greeks and immigrants. CONCLUSION: Adherence to follow-up recommendations is rather poor for all chronic HBV patients. Immigrants are lost more frequently during the first year, but only small proportions of treated and particularly untreated Greek or immigrant patients remain under long-term follow-up.

Reliability and applicability of two-dimensional shear-wave elastography for the evaluation of liver stiffness.

BACKGROUND/AIM: Two-dimensional shear-wave elastography (2D-SWE) is a new elastographic technique that is increasingly being used across several indications. We assessed the reliability and applicability of 2D-SWE in patients with various chronic liver diseases and attempted to identify parameters potentially affecting liver stiffness. METHODS: We included all patients with chronic liver disease who underwent 2D-SWE examination over a 15-month period. Patients with acute hepatitis, active cholestatic disease, or severe heart failure were excluded. The procedures were performed by three adequately trained operators. Standard operating procedures for liver ultrasonography and elastography were followed. RESULTS: 2D-SWE was reliable in 98% of 605 patients. SD to mean liver stiffness value ratio greater than 9.14%, which was considered an indicator of reliability, was associated independently with age more than 50 years, obesity, or overweight, and use of statins for hyperlipidemia. 2D-SWE was applicable, requiring a median time of 7 min per examination and exceeding 15 min in only 5.5% of patients. Worse applicability expressed as duration more than 0.7 min per reliable measurement was associated independently with age more than 50 years and obesity. The mean and median liver stiffness values were 11.6 and 7.7 kPa, respectively. Liver stiffness more than 7.7 kPa was associated independently with age more than 50 years and increased waist circumference. CONCLUSION: 2D-SWE represents an applicable method of assessment of liver fibrosis that can provide reliable results in the vast majority of patients with chronic liver diseases. Older age and obesity may affect the reliability and applicability of the method as well as the severity of liver fibrosis.

Changes in serum transforming growth factor-ß1 levels in chronic hepatitis C patients under antiviral therapy.

BACKGROUND: Several cytokines including transforming growth factor (TGF)-ß1 have been suggested to be involved in the pathogenesis of fibrosis in chronic hepatitis C. We examined the changes of TGF-ß1 serum levels and their predictive value in patients with chronic hepatitis C under antiviral therapy. METHODS: We included 84 patients with chronic hepatitis C who were treated with pegylated interferon-α and ribavirin between 2008 and 2009. Treatment was given for 24-48 weeks depending on HCV genotype. Serum TGF-ß1 levels were measured by an ELISA assay at baseline, at the end of therapy (EOT), and at 6 months after the EOT. Liver fibrosis was evaluated by transient elastography. RESULTS: Of the 84 patients, 76.2% achieved sustained virological response (SVR), 8.3% responded at the EOT but relapsed during post-therapy follow up (RR) and 15.5% had no response (NR). In all patients, mean TGF-ß1 levels were 16,980 pg/mL at baseline and decreased significantly at EOT (12,041 pg/mL) and at 6 months of post-treatment follow up (13,254 pg/mL) (P≤0.001). In particular, mean TGF-ß1 levels decreased significantly from baseline to EOT and to six months of post-treatment follow up in patients with SVR and numerically but not significantly in patients with RR or NR. TGF-ß1 levels were not associated with the severity of liver stiffness estimated by transient elastography. CONCLUSION: Our data show that TGF-ß1 serum levels decrease significantly at the EOT and remain decreased 6 months after the EOT mostly in chronic hepatitis C patients who achieve SVR after pegylated interferon-α and ribavirin combination treatment.

The interferon receptor-1 promoter polymorphisms affect the outcome of Caucasians with HBeAg-negative chronic HBV infection.

BACKGROUND & AIMS: The outcome of HBeAg-negative chronic hepatitis B virus (HBV) patients who may remain in the inactive carrier state (IC) or progress to HBeAg-negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within not only the promoter but also the coding sequence of the interferon receptor 1 (INFAR1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HBeAg-negative patients has not been evaluated. We examined the association of INFAR1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV patients. METHODS: Using a combination of conventional and allele-specific polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis, we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, -408C/T, -3C/T) and one Variable Number Tandem Repeat [VNTR -77(GT)n] within the INFR1 promoter sequence. RESULTS: The genetic polymorphisms examined were found to be associated with the phase of HBeAg-negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes -408CT_-3CT were more likely to be ICs (OR = 2.42 vs. CC, P = 0.036). Also, given the partial linkage between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n ≤ 8/≤8_-568GC and -77(GT)n ≤ 8/≤8_-568CC were detected more frequently among ICs (OR = 11.69, P = 0.005 and OR = 7.56, P = 0.001 vs. -77(GT)n >8/>8_-568GG respectively). CONCLUSIONS: These findings suggest that these genetic variations represent important factors associated with the clinical phase of HBeAg-negative chronic HBV infection.

Elastography for hepatic fibrosis severity in chronic hepatitis B or C.

AIMS: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients. METHODS: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak's classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0-1 (n = 30), 2-3 (n = 20), 4-6 (n = 25), respectively. RESULTS: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p < 0.001). The diagnostic accuracy of elastography for severe fibrosis and cirrhosis was excellent [area under the receiver operating characteristic (AUROC) curve 0.938 vs. 0.948], but it was not optimal for mild fibrosis (AUROC 0.78). Values of 7.5, 9.0 and 12 kPa had a sensitivity and specificity for severe fibrosis/cirrhosis of 96, 84 and 60%, and 76, 90 and 94%, respectively. The median stiffness value in cirrhotic patients (score 5-6) was 16.6 kPa (7.7-48). No differences in accuracy of elastography between CHB or CHC patients were found. Cutoff was 12.5 kPa for cirrhosis; 10/75 patients (13%) were misclassified. CONCLUSION: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation.

Concomitant diagnosis of myeloproliferative neoplasm and non-Hodgkin's lymphoma in a patient with portal vein thrombosis.

We describe here the rare coexistence, at the time of diagnosis, of a myeloproliferative neoplasm (MPN) and non-Hodgkin's lymphoma (NHL) in a 74-year-old patient who presented with thrombocytosis and signs of portal hypertension on physical examination. Abdominal computed tomography scan demonstrated extensive portal vein system thrombosis. Secondary causes of thrombocytosis were excluded. JAK2 V617F mutation was present in the peripheral blood, while bone marrow biopsy revealed marginal zone B-cell lymphoma. Molecular analysis failed to detect BCR-ABL rearrangement in peripheral blood cells. Simultaneous occurrence of MPN and NHL was diagnosed. This case may be of interest not only due to the rare coexistence of PMN and NHL, but also because of the undetermined clinical significance of JAK2 mutation in this subset of patients.